Our laboratory is dedicated to the study of B cell neoplasias containing chromosomal translocations (Tx) which interrupt the c-MYC/PVT 1 region on human chromosome 8 or mouse chromosome 15. This Tx interrupts the transcription of either c-Myc or Pvt 1 and is the principal lesion in many B cell malignancies including Burkitt's lymphoma (BL), AIDs-NHL, mouse plasmacytoma (PCT) and in some cases of Multiple Myeloma (MM). There is a restriction associated with this Tx such that only the immunoglobulin (Ig) heavy chain gene is found juxtaposed to c-Myc and only the Ig light chain gene is found juxtaposed to Pvt 1. Over the past several years, our laboratory has elucidated the structure of the mouse Pvt 1 locus in order to understand the relationship between these two vastly divergeant Txs which, nevertheless, produce indistinguishable disease phenotypes. In the mouse, we have identified a consistent Pvt 1/Ig Ck fusion product which is uniformly found in all tumors harboring Pvt 1 associated chromosomal Txs. Transgenic mice containing Pvt1/Ck and knockout mice defective in the expression of Pvt 1 have been constructed to determine what role Pvt 1 serves in tumor progression as well as in normal development of the mouse. To identify the human analog of Pvt 1, we have looked for DNA rearrangements in samples from patients with MM and BL using DNA probes that span the entire region between human c-MYC and PVT. We have also recently detected a length variation polymorphism in this region of PVT of which one allele is more frequently found in BL patients (suggesting the presence of a susceptibility allele of c-MYC/PVT). Coupled to this study is a similar search for the human PVT gene and the eventual isolation of cDNA clones corresponding to PVT transcripts. Our laboratory has also been instrumental in the detection of somatic point mutations which frequently occur in the coding region of c-MYC in these same B cell tumors. These mutations are clustered in the transactivation domain of exon 2 and co-localize with a region identified as the binding site for both the tumor suppressors, P107 and BIN 1. In a search for c-MYC/PVT 1 cooperating genes, we have also examined p107, the mouse cyclin dependent kinase inhibitor, p21(Waf1) and p53 for co-involvement in B cell tumorigenicity.